The Developmental Landscape of Human Hypothalamus by Single-cell RNA-seq
The hypothalamus comprises various nuclei and neuronal subpopulations that control fundamental homeostasis and behaviors. Even within a certain nucleus, different neuron types show particular gene expression patterns and spatial distribution characteristics, which are closely related to their functions. Our previous work revealed the novel neural stem cell, named hmRG in hypothalamus, that were similar to cortical oRG cells, plays an important role in hypothalamus development (Zhou et al., Nature Communications, 2020). However, spatiotemporal molecular characterization of hypothalamus development in humans is largely unexplored.
Prof. WANG Xiaoqun from the Institute of Biophysics of Chinese Academy of Sciences, together with researchers from Beijing Normal University and the Beijing Anzhen Hospital, Capital Medical University and other collaborators, applied single-cell transcriptional profiling to identify cell types in the developing human hypothalamus and revealed their developmental features. These findings were published online in the journal Cell Stem Cell.
Researchers revealed spatiotemporal transcriptome profiles and cell-type characteristics of human hypothalamus development and illustrated molecular diversity of neural progenitors and the cell fate decision, which is programmed by a combination of transcription factors. Different neuronal and glial fates are sequentially produced and showed spatial developmental asynchrony.
Moreover, human hypothalamic gliogenesis occurs at an earlier stage of gestation and displays distinctive transcription profiles comparing with those in mouse. Notably, early oligodendrocyte cells in humans exhibit different gene patterns and interact with neuronal cells to regulate neuronal maturation by Wnt, Hippo and Integrin signals.
Overall, this study provides a comprehensive molecular landscape of human hypothalamus development at early- and mid-embryonic stages and a foundation for understanding its spatial and functional complexity.
This work was supported by National Basic Research Program of China, the Strategic Priority Research Program of the Chinese Academy of Sciences and the National Natural Science Foundation of China (NSFC).
Contact: WANG Xiaoqun
Institute of Biophysics, Chinese Academy of Sciences
Beijing 100101, China
(Reported by Dr. WANG Xiaoqun's group)